| First Author | Wang CY | Year | 2009 |
| Journal | Sci Signal | Volume | 2 |
| Issue | 62 | Pages | ra11 |
| PubMed ID | 19293429 | Mgi Jnum | J:259097 |
| Mgi Id | MGI:6140853 | Doi | 10.1126/scisignal.2000143 |
| Citation | Wang CY, et al. (2009) Obesity increases vascular senescence and susceptibility to ischemic injury through chronic activation of Akt and mTOR. Sci Signal 2(62):ra11 |
| abstractText | Obesity and age are important risk factors for cardiovascular disease. However, the signaling mechanism linking obesity with age-related vascular senescence is unknown. Here we show that mice fed a high-fat diet show increased vascular senescence and vascular dysfunction compared to mice fed standard chow and are more prone to peripheral and cerebral ischemia. All of these changes involve long-term activation of the protein kinase Akt. In contrast, mice with diet-induced obesity that lack Akt1 are resistant to vascular senescence. Rapamycin treatment of diet-induced obese mice or of transgenic mice with long-term activation of endothelial Akt inhibits activation of mammalian target of rapamycin (mTOR)-rictor complex 2 and Akt, prevents vascular senescence without altering body weight, and reduces the severity of limb necrosis and ischemic stroke. These findings indicate that long-term activation of Akt-mTOR signaling links diet-induced obesity with vascular senescence and cardiovascular disease. |
